title: Toxoplasma gondii soluble tachyzoite antigen triggers protective mechanisms against fatal intestinal pathology in oral infection of C57BL/6 mice.
abstract: Toxoplasma gondii induces a potent IL-12 response early in infection that results in IFN-γ-dependent control of parasite growth. It was previously shown that T. gondii soluble tachyzoite antigen (STAg) injected 48 hr before intraperitoneal infection reduces lipoxin A4 and 5-lipoxygenase (5-LO)-dependent systemic IL-12 and IFN-γ production as well as hepatic immunopathology. This study investigated the ability of STAg-pretreatment to control the fatal intestinal pathology that develops in C57BL/6 mice orally infected with 100 T. gondii cysts. STAg-pretreatment prolonged the animals' survival by decreasing tissue parasitism and pathology, mainly in the ilea. Protection was associated with decreases in the systemic IFN-γ levels and IFN-γ and TNF message levels in the ilea and with increased TGF-β production in this tissue, but protection was independent of 5-LO and IL-4. STAg-pretreatment decreased CD4(+) T cell, NK cell, CD11b(+) monocyte and CD11b(+)CD11c(+) dendritic cell numbers in the lamina propria and increased CD8(+) T cells in the intestinal epithelial compartment. In parallel, decreases were observed in iNOS and IL-17 expression in this organ. These results demonstrate that pretreatment with STAg can induce the recruitment of protective CD8(+) T cells to the intraepithelial compartment and decrease proinflammatory immune mechanisms that promote intestinal pathology in T. gondii infection.
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Benevides
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Cardoso
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Milanezi
authors.forename: Letícia S
authors.initials: LS
authors.lastname: Castro-Filice
authors.forename: Paulo V C
authors.initials: PV
authors.lastname: Barenco
authors.forename: Romulo O
authors.initials: RO
authors.lastname: Sousa
authors.forename: Rosangela M
authors.initials: RM
authors.lastname: Rodrigues
authors.forename: José R
authors.initials: JR
authors.lastname: Mineo
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Neide M
authors.initials: NM
authors.lastname: Silva
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017931:DNA Primers; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; C094052:soluble tachyzoite antigen, Toxoplasma gondii; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse